scholarly journals Molecular characterization of centerin, a germinal centre cell serpin

2007 ◽  
Vol 405 (3) ◽  
pp. 489-494 ◽  
Author(s):  
Melinda A. Paterson ◽  
Anita J. Horvath ◽  
Robert N. Pike ◽  
Paul B. Coughlin
Keyword(s):  
B Cell ◽  
Serine Protease ◽  
Molecular Characterization ◽  
Good Prognosis ◽  
Germinal Centre ◽  
Lymphoid Malignancies ◽  
B Cell Maturation ◽  
Absolute Requirement

Centerin [SERPINA9/GCET1 (germinal centre B-cell-expressed transcript 1)] is a serpin (serine protease inhibitor) whose expression is restricted to germinal centre B-cells and lymphoid malignancies with germinal centre B-cell maturation. Expression of centerin, together with bcl-6 and GCET2, constitutes a germinal centre B-cell signature, which is associated with a good prognosis in diffuse large B-cell lymphomas, but the molecular basis for this remains to be elucidated. We report here the cloning, expression and molecular characterization of bacterial recombinant centerin. Biophysical studies demonstrated that centerin was able to undergo the ‘stressed to relaxed’ conformational change which is an absolute requirement for protease inhibitory activity. Kinetic analysis showed that centerin rapidly inhibited the serine protease trypsin (ka=1.9×105 M−1·s−1) and also demonstrated measurable inhibition of thrombin (ka=1.17×103 M−1·s−1) and plasmin (ka=1.92×103 M−1·s−1). Centerin also bound DNA and unfractionated heparin, although there was no functionally significant impact on the rate of inhibition. These results suggest that centerin is likely to function in vivo in the germinal centre as an efficient inhibitor of a trypsin-like protease.

In vivo characterization of bioconjugate B cell toleragens with specificity for autoantibodies in antiphospholipid syndrome

2003 ◽  
Vol 3 (12) ◽  
pp. 1667-1675 ◽  
Author(s):  
Keith A. Cockerill ◽  
Eric Smith ◽  
David S. Jones ◽  
Michael J. Branks ◽  
Merle Hayag ◽  
...  
Keyword(s):  
B Cell ◽  
Antiphospholipid Syndrome ◽  
In Vivo Characterization

scholarly journals Molecular Characterization of HOXA2 and HOXA3 Binding Properties

2021 ◽  
Vol 9 (4) ◽  
pp. 55
Author(s):  
Joshua Mallen ◽  
Manisha Kalsan ◽  
Peyman Zarrineh ◽  
Laure Bridoux ◽  
Shandar Ahmad ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Molecular Characterization ◽  
Sequence Motif ◽  
Body Parts ◽  
Binding Affinities ◽  
Binding Properties ◽  
Functional Consequences

The highly conserved HOX homeodomain (HD) transcription factors (TFs) establish the identity of different body parts along the antero–posterior axis of bilaterian animals. Segment diversification and the morphogenesis of different structures is achieved by generating precise patterns of HOX expression along the antero–posterior axis and by the ability of different HOX TFs to instruct unique and specific transcriptional programs. However, HOX binding properties in vitro, characterised by the recognition of similar AT-rich binding sequences, do not account for the ability of different HOX to instruct segment-specific transcriptional programs. To address this problem, we previously compared HOXA2 and HOXA3 binding in vivo. Here, we explore if sequence motif enrichments observed in vivo are explained by binding affinities in vitro. Unexpectedly, we found that the highest enriched motif in HOXA2 peaks was not recognised by HOXA2 in vitro, highlighting the importance of investigating HOX binding in its physiological context. We also report the ability of HOXA2 and HOXA3 to heterodimerise, which may have functional consequences for the HOX patterning function in vivo.

scholarly journals NF-κB2 mutation targets TRAF1 to induce lymphomagenesis

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 743-751 ◽  
Author(s):  
Baochun Zhang ◽  
Zhe Wang ◽  
Tai Li ◽  
Erdyni N. Tsitsikov ◽  
Han-Fei Ding
Keyword(s):  
Transgenic Mice ◽  
B Cell ◽  
Apparent Effect ◽  
Antiapoptotic Protein ◽  
Lymphoid Malignancies ◽  
Targeted Expression ◽  
Antiapoptotic Activity ◽  
B Cell Homeostasis ◽  
Cytokine Deprivation

Abstract The NF-κB2 gene is recurrently mutated in human lymphoid malignancies. However, a causal relationship between NF-κB2 mutation and lymphomagenesis has not been established. It is also unclear how the mutation may lead to lymphoid malignancies. We report the generation of transgenic mice with targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, in lymphocytes. The transgenic mice display a marked expansion of peripheral B cell populations and develop predominantly small B cell lymphomas. p80HT expression has no apparent effect on the proliferation of B cells, but renders them specifically resistant to apoptosis induced by cytokine deprivation and mitogenic stimulation. Lymphocytes and lymphoma cells from p80HT mice express high levels of TRAF1, an antiapoptotic protein also implicated in lymphoid malignancies. p80HT binds the TRAF1 promoter in vivo and activates TRAF1 transcription. Moreover, TRAF1 knockdown abrogates the antiapoptotic activity of p80HT and TRAF1 deficiency reestablishes B cell homeostasis in p80HT mice. These findings demonstrate NF-κB2 mutation as an oncogenic event in vivo and suggest a molecular pathway for TRAF1 activation in the pathogenesis of lymphomas.

Molecular characterization of the in vivo alkylating agent resistant murine EMT-6 mammary carcinoma tumors

1995 ◽  
Vol 35 (5) ◽  
pp. 423-431 ◽  
Author(s):  
Devasis Chatterjee ◽  
Chou Jui-Tsai Liu ◽  
David Northey ◽  
Beverly A. Teicher
Keyword(s):  
Molecular Characterization ◽  
Mammary Carcinoma ◽  
Alkylating Agent

scholarly journals Molecular characterization of the grape seeds extract’s effect against chemically induced liver cancer: In vivo and in vitro analyses

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Alaaeldin Ahmed Hamza ◽  
Gehan Hussein Heeba ◽  
Hanan Mohamed Elwy ◽  
Chandraprabha Murali ◽  
Raafat El-Awady ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Molecular Characterization ◽  
Grape Seeds ◽  
Chemically Induced

Molecular characterization of the in vivo effects of the hemorrhagic metalloproteinase HF3: analysis of the proteome of mice muscle tissue

Toxicon ◽  
2019 ◽  
Vol 168 ◽  
pp. S21
Author(s):  
Eric Junqueira Brito Pereira ◽  
Dilza Trevisan Silva ◽  
Solange Maria De Toledo Serrano
Keyword(s):  
Molecular Characterization ◽  
Muscle Tissue ◽  
In Vivo Effects

scholarly journals Characterization of marginal zone B cell precursors

2005 ◽  
Vol 202 (9) ◽  
pp. 1225-1234 ◽  
Author(s):  
Bhaskar Srivastava ◽  
William J. Quinn ◽  
Kristin Hazard ◽  
Jan Erikson ◽  
David Allman
Keyword(s):  
B Cells ◽  
B Cell ◽  
Marginal Zone ◽  
Environmental Cues ◽  
Developmental Potential ◽  
B Cell Maturation ◽  
B Cell Precursors ◽  
Follicular B Cells ◽  
Selection Of

Selection of recently formed B cells into the follicular or marginal zone (MZ) compartments is proposed to occur by way of proliferative intermediates expressing high levels of CD21/35 and CD23. However, we show that CD21/35high CD23+ splenocytes are not enriched for proliferative cells, and do not contribute substantially to the generation of follicular B cells. Instead, ontogenic relationships, steady-state labeling kinetics, and adoptive transfer experiments suggest that CD21/35high CD23+ splenocytes serve primarily as precursors for MZ B cells, although their developmental potential seems to be broader and is influenced by environmental cues that are associated with lymphopenia. Furthermore, CD21/35high CD23+ splenocytes share several key functional characteristics with MZ B cells, including their capacity to trap T-independent antigen and a heightened proliferative response to LPS. These observations challenge previous models of peripheral B cell maturation, and suggest that MZ B cells develop by way of CD21/35high CD23+ intermediates.

scholarly journals Cellular basis for neonatally induced T-suppressor activity. Primary B cell maturation is blocked by suppressor-helper interactions restricted by loci on chromosome 12.

1985 ◽  
Vol 161 (4) ◽  
pp. 816-831 ◽  
Author(s):  
S Raychaudhuri ◽  
M P Cancro
Keyword(s):  
B Cell ◽  
Cellular Mechanism ◽  
Surface Marker ◽  
Cell Maturation ◽  
Chromosome 12 ◽  
Suppressor Activity ◽  
Memory B Cell ◽  
B Cell Maturation ◽  
Th Cell

The cellular mechanism and genetic restriction of neonatally induced HA-specific suppressor T (Ts) cells have been examined. The in vivo effect of these Ts cells on antibody production, primary B cell proliferation, B cell surface marker changes, and helper T (Th) cell priming during primary responses to HA have been determined. The results indicate that, although antigen-induced B cell proliferative responses and surface marker changes occur in the presence of Ts cells, differentiation to Ig secretion, and long-lived memory B cell production are prevented. Further, antigen-specific Th cell priming is completely ablated by Ts cells, suggesting that Ts act by preventing the delivery of Th signals required for both the later stages of primary B cell maturation, and the formation of memory B cell populations. Finally, in vivo cell mixing experiments using congenic mice indicate that this Ts-Th interaction is restricted by loci on mouse chromosome 12.

scholarly journals TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1

Blood ◽  
2017 ◽  
Vol 129 (10) ◽  
pp. 1284-1295 ◽  
Author(s):  
Lorenz Jahn ◽  
Pleun Hombrink ◽  
Renate S. Hagedoorn ◽  
Michel G. D. Kester ◽  
Dirk M. van der Steen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Transcription Factor ◽  
B Cell ◽  
B Cell Malignancies ◽  
High Affinity ◽  
Isolation And Characterization ◽  
Key Points

Key Points Isolation and characterization of a high-affinity TCR targeting the intracellular B cell–specific transcription factor BOB1. T cells expressing a BOB1-specific TCR lysed and eradicated primary multiple myeloma and other B-cell malignancies in vitro and in vivo.

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